Age-Related Macular Degeneration (AMD) is the leading cause of vision loss and blindness in the age group 65 and older. It is estimated that 6 million people in the United States alone are affected and with the aging Baby Boomer population, that figure is expected to grow at an explosive rate. AMD is a progressive disease with increased vision loss as the disease advances, particularly in the advanced stage. Drug companies are actively working to develop medications to slow or stop the advancement of dry AMD. In dry AMD, as opposed to wet AMD, cellular debris called drusen accumulates between the retina and the choroid, and the retina can become detached. There is a great need for a fast, repeatable, clinically-friendly test to serve as an end point in determining the efficacy of dry AMD treatment.
Most vision exams include a high-contrast visual acuity measurement. However, high-contrast visual acuity testing is ineffective in determining the presence or stage of dry AMD. Even advanced dry AMD patients may score at or near 20/20 visual acuity.
AMD patients often report difficulty seeing in dim lighting. “Even in the early stages of the disease when visual acuity is unaffected, these symptoms are present.” Eleonora M. Lad, MD, PhD, Evaluation of visual function impairments in patients with early and intermediate dry age related macular degeneration. Research has shown that night vision loss may precede high-contrast visual acuity loss by two or more years in AMD patients and the difference in day and night vision may be able to not only identify AMD patients but identify the stage of disease as well as serve to be a predictive factor in identifying patients in the highest risk category for VA vision loss.
“The mechanism behind an increased LLD in eyes with AMD is not clearly understood. It has been suggested that [Low-Luminance Visual Acuity] LLVA most likely reflects central cone-mediated function under reduced illumination.” Wu, Zhichao, et al., Low-Luminance Visual Acuity and Microperimetry in Age-Related Macular Degeneration, Article in Press Ophthalmology, 2014. For example, it is suggested that “[i]t is foveal (central) cone function in particular that is the most critical for preservation of (Visual Acuity). A reduction in foveal cone function in dim illumination reduces (Visual Acuity) dramatically.” Janet S. Sunness, MD; Gary S. Rubin, PhD; Aimee Broman, MS; Carol A. Applegate, COT; Neil M. Bressler, MD; Barbara S. Hawkins, PhD, Low Luminance Visual Dysfunction as a Predictor of Subsequent Visual Acuity Loss from Geographic Atrophy in Age-Related Macular Degeneration, Ophthalmology, Volume 115, Number 9, September 2008.
It has also been suggested that night vision loss is “associated with decreased sensitivity of the rod system responsible for vision in the dark. This is consistent with pathology results in eyes with AMD that showed that the rod photoreceptors degenerate earlier than cones in most patients with early AMD, despite good visual acuity.” Id.
A patient's visual function differential from day and night can be measured by comparing high-contrast visual acuity with low luminance visual acuity, or low-luminance deficit (LLD). There is a great need for an automatic, fast, friendly, repeatable Low Luminance Deficit test for use in both clinical trials as well as clinic.
Another study suggests that low luminance cone function may be another predictor of VA loss in AMD. This study reported, “cone dark-adapted function is affected more than cone function under photopic conditions.” Id. “Studies often compare dark-adapted rod function to light-adapted cone function and don't capture cone function in dim illumination.” Id.
This theory is furthered by another study which reports, “eyes with drusen with reduced dark-adapted foveal sensitivity to a small red stimulus, advanced AMD was more likely to develop.” Id. Even though Dark Adaptation, or adapting the eyes to total darkness, has also been shown to be highly diagnostic for early AMD, it is a lengthy process, making it impractical to use in clinic. There is a need for a device to rapidly measure cone function in dim illumination without requiring dark adaptation. Research shows that patients with early AMD have a substantial recovery period for rods and cones to regain function in darkness after being exposed to light, known as “bleaching”, as compared to normal patient population free of eye disease.
Dark Adaptation is a lengthy process, taking 10-20 minutes to complete. The length of time required makes its use in a busy clinic impractical at best.
Currently, two recognized methods exist for measuring Low Luminance Deficit—the early treatment diabetic retinopathy study (ETDRS) light box used with neutral density filters and the Smith Kettlewell Institute Low Luminance Acuity Card (or SKILL Card). Both methods are manual, time consuming, and prone to scoring errors.